PROJECT SUMMARY/ABSTRACT Adolescent girls and young women (ages 15-24 years) have among the highest HIV incidence rates in sub- Saharan Africa. Pre-exposure prophylaxis (PrEP) has the potential to dramatically reduce new HIV infections in this population. However, in several PrEP trials conducted among women in Africa, adherence was too low to result in effectiveness. Substantial knowledge gaps on the drivers of, and how to optimize, adherence to PrEP must therefore be addressed in order to harness the promise of PrEP for young women. The proposed training and research plan in this K23 Mentored Patient-Oriented Research Career Development Award application will allow Catherine Koss, MD to acquire the necessary skills to achieve her career goal of becoming an NIH- funded clinical investigator with expertise in designing and testing HIV prevention interventions, with an emphasis on adherence interventions for women. In this K23 proposal, under the guidance of an expert and dedicated mentoring team, Dr. Koss will use a mixed methods approach to test the central hypothesis that an intervention building on the community adherence club model and tailored to the health needs and priorities of young women will be feasible, acceptable, and ultimately increase adherence to PrEP among young women in East Africa. The community adherence club strategy, in which patients attend group visits led by a health care worker for medication provision and adherence support, is being successfully used in HIV treatment (including among youth) to increase rates of retention in care and viral suppression, but has not yet been adapted for PrEP delivery. This proposal will leverage the resources of an ongoing population-based study that has enrolled over 320,000 individuals in 32 communities in rural Kenya and Uganda to test HIV treatment and prevention strategies (SEARCH, NCT01864603, PI Havlir, K23 primary mentor). SEARCH will provide oral PrEP with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to 6,400 women and men who will be followed at quarterly study visits for monitoring and adherence assessment via objective biological measures (tenofovir concentrations in hair and plasma) and self-report. Building on the candidate's prior research on PrEP and adherence in women, this proposal will address the following specific aims: (1) to elucidate factors influencing adherence to PrEP among young women receiving PrEP in community-based settings in East Africa; (2) to develop a community adherence club intervention to increase adherence to PrEP among young women; (3) to evaluate the feasibility, acceptability, and preliminary effectiveness of the adherence club intervention among young women on PrEP. The proposed research is based on principles of differentiated service delivery and is aligned with Dr. Koss' career development plan to gain expertise in qualitative and mixed methods research and intervention development, testing, and evaluation. The findings of this proposal will lead to an R01 application to test a community adherence club intervention among young women on PrEP in a large-scale trial, with the ultimate goal of reducing the burden of HIV among women worldwide.